INFECTION WITH HELICOBACTER-PYLORI STRAINS POSSESSING CAGA IS ASSOCIATED WITH AN INCREASED RISK OF DEVELOPING ADENOCARCINOMA OF THE STOMACH

To determine whether infection with a Helicobacter pylori strain posse ssing cagA is associated with an increased risk of development of aden ocarcinoma of the stomach, we used a nested case-control study based o n a cohort of 5443 Japanese-American men in Oahu, Hawaii, who had a ph ysical examination and a phlebotomy during 1967 to 1970. We matched 10 3 H. pylori-infected men who developed gastric cancer during a 21-year surveillence period with 103 H. pylori-infected men who did not devel op gastric cancer and tested stored serum specimens from patients and controls for the presence of serum IgG to the cagA product of H. pylor i using an ELISA. The serum IgG assay using a recombinant CagA fragmen t had a sensitivity of 94.4% and a specificity of 92.5% when used in a clinically defined population; serological results were stable for mo re than 7 years. For men with antibodies to CagA, the odds ratio of de veloping gastric cancer was 1.9 (95% confidence interval, 0.9-4.0); fo r intestinal type cancer of the distal stomach, the odds ratio was 2.3 (95% confidence interval, 1.0-5.2), Age <72 years and advanced tumor stage at diagnosis were significantly associated with CagA seropositiv ity. We conclude that infection with a cagA-positive H. pylori strain in comparison with a cagA-negative strain somewhat increases the risk for development of gastric cancer, especially intestinal type affectin g the distal stomach.